This application requests a 5-year renewal of the Center for Environmental Genetics. The unified theme of the proposal is to elucidate how gene and environment interaction through epigenetics influences disease risks and health outcome. Ohioans are exposed to exceptionally bad air quality due to dated power plants and the fact that it is situated in the nation's main artery of the north-south transportation route. These unique geographical/economic features put the residents in the state at high risk of the following diseases: (a) endocrine disruption and cancer; (b) immune and allergic diseases; (c) cardiovascular and lipid disorders; and (d) neurology and behavior disorders. The CEG has 20-years' of accumulative success in environmental health sciences (EHS) research, our aspiration is to help mitigate these environmental diseases, first in Ohio, then extend our success to similar populations in the nation and around the globe. Here we propose to attain our goal by (1) expanding EHS research human capital through the continued recruitment and support of investigators of all levels to EHS research, (2) innovative ideas and collaborative work from new and established investigators will be supported by the Pilot Project Program and Director's Fund, (3) junior investigators will be mentored by a Career Development Program and strong mentor-mentee relationships; (4) an Integrative Technology Support Core combined with a Bioinformatics Core will provide investigators with leading-edge technologies and data analysis to attain a new level of system-biology approach to EHS; (5) enhancement activities such as workshops, symposia and seminar series will be used to stimulate collaboration and innovation; (6) an Integrative Health Sciences Facility Core will provide the toolbox for translation of EHS to the clinical and human studies; and (7) a Community Outreach and Engagement Core will serve to translate EHS to public health and health education for healthier living and disease prevention. The center is led by an outstanding team of directors with visionary scientific and administrative experiences and insights. The team will be assisted by Internal and External Advisory Boards to provide checks and balances. CEG, through cooperation with other centers will strive to expand EHS capacity and beyond.